Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human SNAIL1 (SNAI1) protein encoded by SNAI1/SNA gene represses transcription of E-cadherin/CDH1 gene. Human SNAIL2 (SNAI2) protein encoded by SNAI2/SLUG gene induces the first phase of epithelial-mesenchymal transition (EMT), including desmosome dissociation, cell spreading, and initiation of cell separation. Here, we have identified human SNAIL3 (SNAI3) gene using bioinformatics. Human SNAI3 gene, consisting of at least three exons, spans around the nucleotide position 320214-328221 of human reference genomic contig NT_010404.8 in the reverse orientation. SNAI3 gene, was located between KIAA0233 gene and CBFA2T3 gene in human chromosome 16q24.3, a region affected in breast cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, and therapy-related myeloid leukemia with t(16;21)(q24;q22) translocation. Human SNAI3 gene was found to encode 292-amino-acid polypeptide with the N-terminal SNAG domain and five zinc finger domains. N-terminal SNAG domain was identified in zinc finger proteins SNAI1, SNAI2, SNAI3, SCRATCH (SCRT1), GFI1, and GFI1B. ATP/GTP binding site was identified in SCRT1, GFI1 and GFI1B, but not in SNAI1, SNAI2 and SNAI3. Phylogenetic analysis of human zinc finger proteins with SNAG domain revealed that SNAI1, SNAI2 and SNAI3 were more closely related. These results clearly indicate that SNAI1, SNAI2 and SNAI3 constitute a subfamily among SNAG zinc-finger proteins. Human SNAI3 mRNA was expressed in skin melanotic melanoma, lung epidermoid carcinoma, and germ cell tumor. Because SNAG zinc-finger proteins are transcriptional repressors implicated in carcinogenesis and embryogenesis, SNAI3 gene might be a potent target of pharmacogenomics in the field of oncology and regenerative medicine.
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PMID:Identification and characterization of human SNAIL3 (SNAI3) gene in silico. 1257 45

Hepatic cat scratch disease is rarely reported in liver transplant recipients and has never been reported with discrete liver lesions in the graft. A 52-year-old woman was transplanted for hepatitis C cirrhosis and hepatocellular carcinoma. Her posttransplant course was uneventful. She presented 2.7 years after transplantation with fever of unknown origin and went on to develop multiple and diffuse discrete liver lesions. Despite an extensive work-up including percutaneous and laparoscopic biopsies, a subsegmental resection that included one of these masses was required to make the diagnosis of Bartonella henselae infection. Serologic tests were equivocal. Histology was consistent with cat scratch disease of the liver, and polymerase chain reaction (PCR) testing of the resected tissue confirmed the diagnosis. Response to doxycycline was rapid. Fevers resolved within 7 days. Repeat abdominal CT scan showed reduction of the liver masses. Cat scratch disease should be considered in postliver transplant patients presenting with fever and liver lesions, especially if close contact with cats has occurred. Diagnosis by PCR testing of involved tissue is preferred when serologies are equivocal due to immunosuppression.
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PMID:Cat scratch disease causing hepatic masses after liver transplant. 1724 93

The invasive and metastatic potentials of hepatocellular carcinoma are positively correlated with the expression level of alpha3beta1 integrin, a high-affinity adhesion receptor for laminin isoforms including laminin-5. In this study, we investigated changes in the adhesive and invasive behaviors of human HCC HepG2 cells after transfection with cDNA for alpha3 integrin in order to elucidate the direct involvement of this integrin in these cellular processes. We introduced cDNA for splice variants of alpha3 integrin (alpha3A and alpha3B) into the cells, and selected two transfectant clones (HepG2-3A and HepG2-3B), which express the alpha3A and alpha3B integrins, respectively. Both transfectant cells adhered almost equally to laminin-5-coated plates in an alpha3 integrin-dependent manner, indicating that transfected alpha3Abeta1 and alpha3Bbeta1 integrins were functionally active in these cells. The migratory and invasive potentials of the transfectant cells were assessed by scratch wound assay and in vitro chemoinvasion assay. The results demonstrated that the migration of HepG2-3A and HepG2-3B cells but not of mock transfectant (HepG2-M) cells was stimulated on the plates coated with laminin-5. Furthermore, HepG2-3A and HepG2-3B cells were found to be more invasive into laminin-5-containing matrices than were HepG2-M cells. These results strongly suggest that enhanced expression of alpha3beta1 integrin on HCC cells is directly involved in their malignant phenotypes such as invasion and metastasis.
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PMID:Changes in adhesive and migratory characteristics of hepatocellular carcinoma (HCC) cells induced by expression of alpha3beta1 integrin. 1799 26

The Sonic hedgehog (SHh) pathway plays a critical role in normal embryogenesis and carcinogenesis, but its function in cancer cells treated with 5-fluorouracil (5-FU) remains unknown. We examined the expression of a subset of SHh signaling pathway genes, including SHh, SMO, PTC1, Su(Fu) and HIP in human hepatocellular carcinoma (HCC) cell lines, Hep3B and HepG2, treated with 5-FU by reverse transcription-polymerase chain reaction. Using trypan blue analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay, we also detected the apoptosis of Hep3B cells resulting from the transfection of pCS2-Gli1 expression vector combined with 5-FU treatment. The motility of the cells was detected by scratch wound closure assay. The expression and subcellular location of PTC1 protein in Hep3B cells treated by 5-FU were also investigated by Western blot analysis and immunofluorescent microscopy. The results indicated that the expression of SHh pathway target molecules at both messenger RNA and protein levels are evidently down-regulated in Hep3B cells treated with 5-FU. The overexpression of Gli1 restores cell viability and, to some extent, the migration abilities inhibited by 5-FU. Furthermore, 5-FU treatment affects the subcellular localization of PTC1 protein, a key member in SHh signaling pathway. Our data showed that the down-regulation of SHh signaling pathway activity was involved in 5-FU-induced apoptosis and the inhibition of motility in hedgehog-activated HCC cell lines. This implies that the combination of SHh signaling pathway inhibitor and 5-FU-based chemotherapy might represent a more promising strategy against HCC.
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PMID:Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells. 1877 95

Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. However, the role of DCP in the development of angiogenesis is not well understood. Herein, we report the effects of DCP on growth and migration of human vascular endothelial cells. DCP significantly stimulated the proliferation of HUVEC (ECV304) cells in a dose and time dependent manner, as measured by the MTT assay. A continuous rapid migration of ECV304 cells was observed in the presence of DCP measured by the scratch wound assay. The continuous rapid invasive activity, measured by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix (Matrigel). Further, the tube formation of vascular endothelial cells on 3-D Matrigel showed an increased number of branch points of ECV304 cells induced by DCP in a dose dependent manner. The levels of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were also examined. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these data suggest that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities in angiogenesis of HCC.
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PMID:Des-gamma-carboxy prothrombin stimulates human vascular endothelial cell growth and migration. 1926 29

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Most patients with HCC die within one year after diagnosis largely because of frequent tumor recurrence and metastasis. The tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) is one of the most commonly lost or mutated genes in a variety of human cancers, including HCC. PTEN antagonizes phosphoinositide-3-kinase (PI3K)/ATP-dependent tyrosine kinase (Akt) signaling, thereby negatively regulating a multitude of biological aggressive tumor behaviors. However, the direct role and mechanism of PTEN in the regulation of invasion and invasion-related gene expression in HCC remain to be elucidated. In this study, we introduced wild-type PTEN or phosphatase-dead PTEN into HepG2 cells that have low expression of PTEN. We found that overexpression of PTEN inhibits HepG2 cell growth via cell cycle arrest without inducing apoptosis. Matrigel invasion and scratch assays indicated that PTEN significantly inhibits HepG2 cell migration and invasion in vitro. On the molecular level, overexpression of PTEN suppressed expression of matrix metalloproteinase (MMP)-2 and -9 in HepG2 cells. Similarly, treatment of HepG2 cells with the PI3K/Akt pharmacological inhibitor, LY294002, potently suppressed cell migration and invasion as well as expression of MMPs. However, the phosphatase-dead PTEN mutant did not exert the same effects. Our data show that PTEN not only inhibits HepG2 cell growth via cell cycle arrest, but also suppresses cell invasion in a PI3K/Akt/MMP-dependent manner, which suggests that loss or mutation of PTEN may contribute to increased cell invasion and facilitates HCC progression.
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PMID:PTEN inhibits the migration and invasion of HepG2 cells by coordinately decreasing MMP expression via the PI3K/Akt pathway. 2042 14

This study is to find out the induction by sodium nitrite of epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma cells, SMMC-7721. After treatment of SMMC-7721 with 0.25 - 25 mmol.L-1 sodium nitrite for 48 h, the assays used include enzyme-linked immunosorbent assay (ELISA) for evaluation of TGF-beta1, IL-6 and IL-8 level in the conditioned medium, phase-contrast microscopy for morphology observation, and scratch wound healing as well as transwell migration assays for measurement of migration and metastatic potential. Additionally, the hallmarks of EMT, p-AKT and its downstream signaling molecules were examined by Western blotting. The results showed that TGF-beta1 secreted by SMMC-7721 elevated significantly in a dose-dependent fashion, whereas the increased IL-8 and IL-6 did not show dose-dependent response. The EMT was induced by exposure of SMMC-7721 with 0.25 mmol.L-1 of sodium nitrite, which was characterized by increased level of Vimentin, decreased E-cadherin and elevated activity of migration and metastatic potential. The results suggest that sodium nitrite could induce SMMC-7721 EMT by increased secretion of TGF-beta1 and IL-8.
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PMID:[Sodium nitrite induces epithelial-mesenchymal transition of SMMC-7721 cells]. 2180 May 36

hsa-miR-191 is highly expressed in hepatocellular carcinoma (HCC), but the factors regulating this elevated expression are unknown. This study aimed to investigate the epigenetic mechanisms of increased hsa-miR-191 expression by analyzing the relationship between the DNA methylation status of hsa-miR-191 and miR-191 expression. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing PCR, Northern blot, and quantitative real-time PCR were performed to examine hsa-miR-191 methylation and expression levels. Western blot, transwell, and scratch assays were performed to examine the function and molecular mechanisms of hsa-miR-191. Approximately 58.9% of hsa-miR-191 expression was higher in HCC tissues than in adjacent noncancerous tissues; this high expression was associated with poor prognosis. The hypomethylation observed in some HCC cell lines and HCC tissues was correlated with the hsa-miR-191 expression level. This correlation was validated by treatment with the 5-aza-DAC demethylation agent. The level of hypomethylation was 63.0% in 73 clinical HCC tissue samples and was associated with increased (2.1-fold) hsa-miR-191 expression. The elevated expression of hsa-miR-191 in the SMMC-771 HCC cell line induced the cells to transition into mesenchymal-like cells; they exhibited characteristics such as loss of adhesion, down-regulation of epithelial cell markers, up-regulation of mesenchymal cell markers, and increased cell migration and invasion. Inhibiting hsa-miR-191 expression in the SMMC-7721 cell line reversed this process (as assessed by cell morphology and cell markers). Furthermore, hsa-miR-191 probably exerted its function by directly targeting TIMP metallopeptidase inhibitor 3 and inhibiting TIMP3 protein expression. Our results suggest that hsa-miR-191 locus hypomethylation causes an increase in hsa-miR-191 expression in HCC clinical tissues and that this expression induces HCC cells to transition into mesenchymal-like cells.
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PMID:Hypomethylation of the hsa-miR-191 locus causes high expression of hsa-mir-191 and promotes the epithelial-to-mesenchymal transition in hepatocellular carcinoma. 2196 17

Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme that regulates many important biological processes, including cell migration, viral infection and autophagy. The aim of this study was to investigate the significance of HDAC6 in the invasion and metastasis activities of hepatocellular carcinoma (HCC). Three HCC cell lines and two primary cultures of hepatocytes were used for biological experiments. Immunohistochemistry for HDAC6 protein was also examined in 70 resected primary HCCs. Knockdown of the HDAC6 gene in the HCC cell lines was carried out by treatment with siRNA, and their migration and invasion activities were examined by the scratch assay and Matrigel invasion assay, respectively. HDAC6 expression was greater in all of the HCC cell lines compared to the primary cultures of hepatocytes. Knockdown of HDAC6 markedly downregulated the migration and invasion activities of all HCC cell lines (P<0.05). Overexpression of HDAC6 protein to a level higher than that in the corresponding normal hepatocytes was observed in 14 (20%) of the 70 primary HCCs, and was significantly correlated with high clinical stage, number of tumors, vascular invasion and intrahepatic metastasis (P<0.05). These results suggest that overexpression of the HDAC6 protein is involved in the migration and invasion activities of HCC cells, and may be a good biomarker for prediction of intrahepatic metastasis.
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PMID:Overexpression of histone deacetylase 6 contributes to accelerated migration and invasion activity of hepatocellular carcinoma cells. 2276 42

To explain biological function of protein CCL15 in HCC cell lines. The different expression level of CCL15 among HCC cell lines was validated by RT-PCR and Western blot. The expression recombinant plasmid of siRNA-CCL15 was constructed successfully and transfected into high metastasis cell lines HCCML3 to observe the alteration of biological function of HCCML3. The overexpression of CCL15 in high metastasis HCC cell lines was confirmed by validation tests. After transfected with siRNA-CCL15, the average amounts of invaded cells in cell invasion assay were 657.9 (HCCML3) and 148.4(HCCML3-siCCL15) (t=19.34, P less than 0.05). And in the scratch assay, the migrating distance were (0.35+/-0.02) mm (HCCML3) and (0.82+/-0.03)mm (HCCML3-siCCL15) (t=15.67, P less than 0.05). The expression of MMP-9 in HCCML3 was higher than HCCML3-siCCL15 through Western blot. Some biological properties (migration, invasion, MMP-9) of HCCML3 transfected with siRNA-CCL15 were decreased. The results suggest CCL15 might play an important role in HCC cell invasion and metastasis through two paths of MMPs regulation and invasion potential strengthening.
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PMID:[Biological function explore of protein CCL15 in HCC cell lines]. 2297 Dec 84


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